Clinical Trial of PXD101 in Patients With Advanced Multiple Myeloma

Inclusion criteria

• Signed informed consent
• A confirmed diagnosis of multiple myeloma, diagnostic criteria as follows, in patients who have failed at least two prior lines of therapy.

Diagnostic criteria for multiple myeloma:

A Monoclonal immunoglobulin (M-component) in serum of IgG-type > 30 g/l, of IgA type > 20 g/l, of IgD type or IgE type of any concentration and/or excretion of M-component in the urine of type k or l type > 1 g/24 hours.

B M-component in serum and/or urine in lower concentration than indicated above in 'A'.

C 10% or more plasma cells in bone marrow aspirate or plasmocytosis in biopsy from bone marrow or soft tissue tumor D Osteolytical bone lesions.

The diagnosis of multiple myeloma demands one of the following combinations: A+C, A+D, or B+C+D.

• Evaluable disease (as defined above)
• Adequate bone marrow and hepatic functions including the following:

• WBC > 2.5 x 109/l, absolute neutrophil count ≥ 1.5 x 109/l, platelets ≥ 50x109/l
• Total bilirubin ≤1.5 x upper normal limit.
• AST (SGOT), ALT (SGPT) ≤2.5 x upper normal limit
• Serum potassium within normal range.
• Age ≥18 years
• Performance status (PS) ≤2 (ECOG scale)
• Estimated life expectancy greater than 3 months
• Female patients with reproductive potential with a negative serum pregnancy test within the last 7 days before trial enrollment and use a safe contraceptive during and in a period of 60 days after the trial. Fertile female partners to male participants must likewise use contraceptive.

Exclusion criteria

• Anticancer therapy including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents within the last 4 weeks or a longer period depending on the defined characteristics of the agents used (e.g. 6 weeks for mitomycin or nitrosourea). Exception: bisphosphonates for bone disease caused by multiple myeloma.
• Active infection or any medical condition likely to interfere with trial procedures.
• Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension, congestive heart failure related to primary cardiac disease, a condition requiring anti-arrhythmic therapy, ischemic or severe valvular heart disease, or a myocardial infarction within 6 months prior to the trial entry.
• A marked baseline prolongation of QT/QTc interval, e.g., repeated demonstration of a QTc interval >500; Long QT Syndrome; the required use of concomitant medication on PXD101 infusion days that may cause Torsade de Pointes. (See Appendix B for list).
• Patients with renal insufficiency defined as a calculated creatinine clearance of < 45 ml/min.
• Clinically significant central nervous system disorders requiring neuroleptics or anti-convulsant medication.
• Altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies
• Other malignant diseases requiring treatment
• Non-secretory multiple myeloma or symptomatic amyloidosis
• Pregnant or breast-feeding women
• Women of childbearing age and potential, who do not use effective contraception
• Known HIV positivity